Several invasive and noninvasive techniques are used to assess patients with known or suspected coronary artery disease. Included among the noninvasive methodologies are electrocardiography, radionuclide angiography (first pass and equilibrium studies utilizing, for example, technecium 99 m labeled red blood cells), myocardial perfusion scintigraphy (utilizing positron emitting radiopharmaceuticals, for example, thallium-201, rubidium-82, nitrogen-13), and echocardiography (M mode and two dimensional). The manifestations of coronary artery disease are a function of the balance between myocardial oxygen supply and demand. Although these noninvasive procedures may be performed in a resting subject, there may not be sufficient imbalance between supply and demand to detect abnormalities at rest. Therefore, provocative studies are frequently performed to improve the predictive accuracy of these diagnostic procedures. The most commonly employed provocative (stress) technique utilizes a standard exercise protocol. Under conditions of exercise myocardial oxygen demand is increased to exceed supply. This form of stress testing is commonly employed in conjunction with electrocardiography, radionuclide angiography, myocardial perfusion scintigraphy, echocardiography, and contrast ventriculography.
Recently, provocative studies have been developed utilizing pharmacological techniques designed to increase myocardial oxygen supply. Specifically, coronary vasodialators (e.g. nitrates, papavarine, dipyridamole, etc.) have been used for this purpose, although none have been approved by the FDA for this specific indication. While the mechanism is not clear, these agents may dilate normal vessels to a greater extent than diseased vessels, establishing a shunt or "myocardial steal". Pharmacological provocation may be particularly useful in patients who are unable to exercise, and may be equal to or superior to exercise provocation in patients capable of exercising. Furthermore, since exercise increases demand and coronary vasodilators increase supply, it is possible that the highest diagnostic yield will accrue when they are used in conjunction with one another.
Coronary arteriography is an invasive procedure which currently represents the "gold standard" for confirming the diagnosis of coronary artery disease. However, this procedure only establishes the anatomical severity of the disease and provides little information concerning the functional significance of visible lesions. Furthermore, small vessel disease may be present and beyond the resolution of currently available equipment. Recently, in an attempt to establish the functional significance of coronary lesions, coronary vasodilators have been administered by intracoronary injection or intravenous infusion and coronary blood flow is measured by one of several techniques, such as doppler flow catheters, videodensitometry, coronary sinus thermodilution, and radionuclide clearance of inert gases. These techniques are becoming more widely used to measure coronary flow reserve (i.e. reserve capacity) which provides important information concerning the functional significance of stenotic vessels. Although nitrates, papavarine, and dipyridamole have been used by some physicians for this purpose, no vasodilator has been approved by the FDA for this specific indication. The use of adenosine, 1-methyl-2-phenylethyl-adenosine, 5-ethyl carboxamide adenosine, cyclopentyl adenosine 2-chloro adenosine, adenine, inosine, adenosine monophosphate, adenosine diphosphate, or adenosine triphosphate, in conjunction with the above stated techniques to measure coronary flow reserve and assess the functional severity of stenotic vessels represents a novel application (indication) of our compound.